Solid dispersions of insoluble drug and preparation method thereof

Patent metadata

Field	Value
Publication number	US-9566268-B2
Application number	US-201615231382-A
Country	US
Kind code	B2
Filing date	Aug 8, 2016
Priority date	Nov 7, 2012
Publication date	Feb 14, 2017
Grant date	Feb 14, 2017

Abstract

The present invention relates to a solid dispersion characterized in that it comprises carbamic acid 3-(4-benzyloxy-phenyl)-isoxazol-5-ylmethyl ester as an active ingredient and a water-soluble polymer having a glass transition temperature lower than the melting point of the active ingredient as a carrier, and it is prepared via melt extrusion. The solid dispersion of the present invention remarkably increases the solubility and dissolution rate of the active ingredient which is an insoluble drug to efficiently improve the bioavailability when it is orally administered.

First claim

What is claimed is:

1. A method for treating a disease of central nervous system, comprising administering to a patient in need thereof a pharmaceutically effective amount of a solid dispersion comprising:
10 to 50 wt % carbamic acid 3-(4-benzyloxy-phenyl)-isoxazol-5-ylmethyl ester, or a pharmaceutically acceptable salt thereof,
45 to 85 wt % water-soluble polymer having a glass transition temperature lower than the melting point of carbamic acid 3-(4-benzyloxy-phenyl)-isoxazol-5-ylmethyl ester, and
1 to 5 wt % plasticizer,
wherein the solid dispersion is prepared by melt extrusion,
wherein the water-soluble polymer is selected from polyvinylpyrrolidone, hypromellose acetate succinate and a combination thereof,
wherein the plasticizer is selected from the group consisting of D-alpha-tocopheryl polyethylene glycol 1000 succinate, polyethylene glycol 400, and a combination thereof,
and wherein the disease of central nervous system is a disease selected from the group consisting of ictus, Alzheimer's disease, Huntington's disease, Parkinson's disease, Pick's disease, Creutzfeld-Jacob disease, Parkinson-ALS-dementia complex of Guam, Wilson's disease, multiple sclerosis, progressive supranuclear palsy, neuropathic pain and bipolar disorder, corticobasal degeneration, schizophrenia, attention deficit hyperactivity disorder, dementia, amyotrophic lateral sclerosis, retinal disease, epilepsy, stroke, transient ischemic attacks, myocardial ischemia, myoischemia, ischemia caused by surgical technique associated with the extended stoppage of cerebral blood flow, head trauma, spinal cord trauma, hypoxia and depression.

2. The method of claim 1 , wherein the solid dispersion is administered orally.

3. The method of claim 1 , wherein the solid dispersion comprises:
about 30 wt % of carbamic acid 3-(4-benzyloxy-phenyl)-isoxazol-5-ylmethyl ester,
about 69 wt % of polyvinylpyrrolidone, and
about 1 wt % of D-alpha-tocopheryl polyethylene glycol 1000 succinate.

4. The method of claim 1 , wherein the solid dispersion comprises:
about 30 wt % of carbamic acid 3-(4-benzyloxy-phenyl)-isoxazol-5-ylmethyl ester,
about 69 wt % of polyvinylpyrrolidone, and
about 1 wt % of polyethylene glycol 400.

5. The method of claim 1 , wherein the solid dispersion comprises:
about 15 wt % of carbamic acid 3-(4-benzyloxy-phenyl)-isoxazol-5-ylmethyl ester,
about 84 wt % of hypromellose acetate succinate, and
about 1 wt % of polyethylene glycol 400.

6. The method of claim 1 , wherein the solid dispersion comprises:
about 50 wt % of carbamic acid 3-(4-benzyloxy-phenyl)-isoxazol-5-ylmethyl ester,
about 40 wt % of hypromellose acetate succinate, and
about 10 wt % of D-alpha-tocopheryl polyethylene glycol 1000 succinate.

7. The method of claim 1 , wherein the solid dispersion melts at a temperature lower than the melting point of carbamic acid 3-(4-benzyloxy-phenyl)-isoxazol-5-ylmethyl ester.

Assignees

• Sk Biopharmaceuticals Co Ltd

Inventors

• Baek Myoung Ki
• Pegan Augustin

Classifications

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61K9/2031

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers · CPC title

• A61K9/146 Primary

  with organic macromolecular compounds · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title